Antibody Peptide Based Antifungal Immunotherapy

Abstract

Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents. In this topic, the search path from the study of the yeast killer phenomenon to the production of Ab-derived peptides characterized by in vitro and in vivo fungicidal activity will be focused. In particular, Abs that mimic the antimicrobial activity of a killer toxin (“antibiobodies”) and antifungal peptides derived from antibiobodies (killer peptide) and other unrelated Abs [complementarity determining regions (CDR)-based and constant region (Fc)-based synthetic peptides] are described. Mycological implications in terms of reevaluation of the yeast killer phenomenon, roles of antibiobodies in antifungal immunity, of β-glucans as antifungal targets and vaccines, and of Abs as sources of an unlimited number of sequences potentially active as new immunotherapeutic tools against fungal agents and related mycoses, are discussed.

The Mechanistic Targets of Antifungal Agents: An Overview

“…The most common opportunistic pathogenic fungi include the Candida species, Cryptococcus neoformans (sometimes referred to as Filobasidiella neoformans ), the Aspergillus species, Histoplasma capsulatum, Coccidioides imitis and the Fusarium species [2–4]. As a result of the increasing prevalence of these life threatening systemic mycoses, [5] there is a continuing need for novel antifungal agents not only to treat the common pathogens but also for resistant fungi associated with the immunosuppressant conditions used during solid organ transplants [6]. Classified as eukaryotes, fungal cells present several similarities with mammalian cells including the fact that their cell nucleus contains DNA organized into chromosomes.…”

Water-soluble polysaccharide isolated with alkali from the stem of Physalis alkekengi L.: Structural characterization and immunologic enhancement in DNA vaccine

“…Systemic candidiasis arises as a result of a normal commensal fungus when the normal microflora balance is disrupted in the host (LeibundGut-Landmann, Wüthrich, & Hohl, 2012;Magliani et al, 2012;Vecchiarelli, Pericolini, Gabrielli, & Pietrella, 2012). Over the past two decades, morbidity and mortality of systemic candidal infection has increased significantly even in the presence of antifungal therapy (Gudlaugsson et al, 2003).…”

Vaccines and immunotherapy against fungi: the new frontier

“…A therapeutic monoclonal antibody in early phase research for sporotrichosis is also detailed (Almeida, 2012). Moreover, the broad potential of antibody-derived “killer peptides” is presented (Magliani et al, 2012). Finally, new information about the antifungal activity of “old” drugs is discussed.…”